Pyrrole-Annulated Heterocyclic Systems. Synthesis of 2H-Pyrrolo[3,4-b][1,5]benzothiazepine 4,4-Dioxide Derivatives

Condensation of 2-nitrothiophenol with ethyl propiolate afforded 3-(2-nitrophenylthio)propenoate. Oxidation of sulfur atom to sulfone group gave ethyl 3-(2-nitrophenylsulfonyl)propenoate, which underwent condensation with tosyl methylisocyanide (TosMIC) to yield ethyl 4-(2-nitrophenylsulfonyl)pyrrole-3-carboxylate. Reduction of nitro group afforded ethyl 4-(2-aminophenylsulfonyl)-1H-pyrrole-3-carboxylate, which was cyclized to 2H-pyrrolo[3,4-b][1,5] benzothiazepin-10(9H)-one 4,4-dioxide. Similar procedure was used for the synthesis of 9,10-dihydro-10-methyl-2H-pyrrolo[3,4-b][1,5]benzothiazepine 4,4-dioxide.     

Synthesis of azoles based on N,N′-bis(hydrazinocarbonyl-ethyl)-1,4-phenylenediamine

N,N′-Bis[(1-methyl-3-oxobutylidene)hydrazinocarbonylethyl]-, N,N′-bis[(2,5-dimethylpyrrol-1-yl)carbamoylethyl]-, N,N′-bis(phenylureidocarbamoylethyl)-, N,N′-bis(phenylcarbamoyl)-, N,N′-bis(phenylureidocarbamoylethyl)-, and N,N′-bis[(4,5-dihydro-5-oxo-4-phenyl-1,2,4-triazol-3-yl)ethyl]-1,4-phenylene-diamines, and their thio analogs were obtained by the condensation of N,N′-bis-(hydrazinocarbonylethyl)-1,4-phenylenediamine with 2,4-pentanedione, 2,5-hexanedione, phenyl isocyanates, or phenyl isothiocyanates (with subsequent treatment of the obtained semicarbazides with alkali), and carbon disulfide respectively.     

Mannich reaction of pyrrole and dimethylpyrrole with monoamines and diamines

The Mannich reaction of pyrrole with ethylenediamine dihydrochloride and formaldehyde gave two compounds: N¹,N¹,N²,N²-tetrakis(pyrrol-2-ylmethyl)ethane-1,2-diamine 1 and 1,3-bis(pyrrol-2-ylmethyl)imidazolidine 2 in poor yields. Conversely, the reaction of pyrrole with propylenediamine dihydrochloride afforded macrocyclic compound 3 containing two pyrrole rings bridged by two dimethylenehexahydropyrimidine moieties in 50% yield. The reaction of 2,5-dimethylpyrrole with methylamine hydrochloride and formaldehyde gave novel bicycle 4 consisting of a dimethyltetrahydro-1,3-diazepine ring fused with a 2,5-dimethylpyrrole ring. The reaction of 2,5-dimethylpyrrole with ammonium chloride gave the tripodal ligand tris(2,5-dimethylpyrrol-3-yl)methylamine 5 in 62% yield. The structures of 2–4 were determined by single crystal X-ray diffraction studies.     

Reformatsky Reaction of Methyl 1-Bromocycloalkanecarboxylates with α-Dicarbonyl Compounds

Reformatsky reactions of methyl 1-bromocyclohexanecarboxylate and methyl 1-bromocyclo-pentanecarboxylate with 2-aryl-2-oxoacetaldehydes involve both carbonyl groups of the latter and result in formation of 3a-aryl-3,3 : 6,6-bis(pentamethylene)- and 3a-aryl-3,3 : 6,6-bis(tetramethylene)tetrahydrofuro-[3,2-b]furan-2,5-diones. The reaction with 2-(2,4-dimethylphenyl)-2-oxoacetaldehyde gives acyclic products, methyl 1-[1-hydroxy-2-(2,4-dimethylphenyl)-2-oxoethyl]cyclohexanecarboxylate and methyl 1-[1-hydroxy-2-(2,4-dimethylphenyl)-2-oxoethyl]cyclopentanecarboxylate, while with benzil methyl 1-(4-hydroxy-1-oxo-3,4-diphenyl-2-oxaspiro[4.5]dec-3-yl)cyclohexanecarboxylate and methyl 1-(4-hydroxy-1-oxo-3,4-diphenyl-2-oxaspiro[4.4]non-3-yl)cyclopentanecarboxylate are obtained.     

Photochromic dihetarylethenes. 13. Optimization of conditions for the acylation of 2,5-dimethylthiophene with squaric acid dichloride

The conditions for acylation of 2,5-dimethylthiophene with squaric acid dichloride were optimized, and 3,4-bis(2,5-dimethylthiophen-3-yl)cyclobut-3-ene-1,2-dione was obtained in good yield. X-ray diffraction analysis demonstrated that the by-product has the structure of 1a,1b-dichloro-5-(2,5-dimethylthiophen-3-yl)-3-hydroxy-4,5a-dimethyl-1b,4a,5,5a-tetrahydro-1aH-1-thiacyclopropa[a]pentalen-2-one.     

Cyclization of vicinally substituted heterocyclic analogs of 3,4-bis(indol-1-yl)maleimide under the action of protic acids: a quantum chemical study

B3LYP/6-31G(d) density functional quantum chemical calculations of vicinally substituted bis(indol-1-yl)derivatives of 1,5-dihydropyrrol-2-one, furan-2,5-dione, cyclopent-4-ene-1,3-dione, cyclobut-3-ene-1,2-dione, and pyrrolidine-2,5-dione were carried out to study the effect of modification of the maleimide moiety in 3,4-bis(indol-1-yl)maleimides on the direction of intramolecular cyclization under the action of protic acids. Geometric parameters, charge distributions, energy characteristics, and frontier orbital energies of these compounds and the corresponding indoleninium cations were determined. Alternative protonation routes of 3,4-bis(indol-1-yl)-1,5-dihydropyrrol-2-one have been studied. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1348–1352, July, 2008.     

Synthesis of trifluoromethyl derivatives of alkyl 2-nitromethylphosphonopropionates and -phosphonobutyrates

By adding diethyl hydrogen phosphite to 5-trifluoromethyl-2-furaldehyde (5-trifluoromethylfur-2-yl)(diethoxyphosphoryl)methanol was synthesized. It was oxidized with DMSO-acetic anhydride mixture to diethyl 5-trifluoromethyl-2-furoyl phosphonate. The reaction of the latter with ethoxymethylenetriphenylphosphorane gives ethyl (2E)-3-(diethoxyphosphoryl)-3-(5-trifluoromethylfur-2-yl)propenoate. Analogous reaction of (diethoxyphosphoryl)(5-trifluoromethylfur-2-yl)acetic aldehyde yields ethyl (4E)-4-(diethoxyphosphoryl)-4-(5-trifluoromethylfur-2-yl)-but-3-enoate. The addition of nitromethane to these esters of unsaturated acids in the presence of potassium fluoride gives a mixture of diastereomers of phosphorylated esters of 2-nitromethyl-3-(5-trifluoromethylfur-2-yl)propanoic and 3-nitromethyl-4-(5-trifluoromethylfur-2-yl)butanoic acids respectively. By the reduction of ethyl nitropropanoate with zinc and formic acid in dioxane ethyl 2-aminomethyl-3-(diethoxyphosphoryl)-3-(5-trifluoromethylfur-2-yl)propanoate was prepared in a low yield. It may be considered as the derivative of β-alanine containing additional pharmacophore fragments.     

Condensation reactions of a comenaldehyde derivative

Condensation reactions of comenaldehyde methyl ether (I) with malonic acid, ethyl cyanoacetate, and cyanoacetamide to give β-(5-methoxy-4H-pyran-4-on-2-yl)acrylic acid (II), ethyl 2-cyano-3-(5-methoxy-4H-pyran-4-on-2-yl)propenoate (III), and 2-cyano-3-(5-methoxy-4H-pyran-4-on-2-yl)propenamide (IV), respectively, are described. Ultraviolet absorption spectra for 2-hydroxymethyl-5-methoxy-4H-pyran-4-one, I and II are presented.     

Efficient synthesis of functionalized spiro-2,5-dihydro-1,2-λ-oxaphospholes

The reaction of ethyl propiolate with triphenylphosphine (Ph₃P) in the presence of N-alkylisatins led to ethyl 2,2,2-triphenyl-2,5-dihydro-1,2-λ⁵-oxaphosphole-4-carboxylate-spiro-1-alkyl-1,3-dihydro-2H-indol-2-ones in good yield. The reaction of dialkyl acetylenedicarboxylates with Ph₃P in the presence of N-alkylisatins led to dialkyl 2,2,2-triphenyl-2,5-dihydro-1,2-λ⁵-oxaphosphole-3,4-dicarboxylate-spiro-1-alkyl-1,3-dihydro-2H-indol-2-ones and alkyl 4-(alkoxy)-5-oxo-2,5-dihydro-3-furancarboxylate-spiro-1-alkyl-1,3-dihydro-2H-indol-2-ones.     

Synthesis and properties of dihetaryl-substituted furanones. Synthesis of photochromic dithienylethenes containing a furanone bridging fragment

The reaction of 2,5-dimethylthiophen-3-ylacetic acid with 2,5-dimethylthiophen-3-ylacetyl chloride gave 3,4-bis(2,5-dimethylthiophen-3-yl)furan-2(5H)-one which was converted into a series of 5-methylidene and 5-arylmethylidene derivatives.     

Synthesis and Transformations of Ethyl (Z)-2-(2,3-dihydro-1,3-dioxo-1H-isoindol-2-yl)-3-(dimethylamino)propenoate

Ethyl (Z)-2-(2,3-dihydro-1,3-dioxo-1H-isoindol-2-yl)-3-(dimethylamino)propenoate was prepared in one step from ethyl (2,3-dihydro-1,3-dioxo-1H-isoindol-2-yl)acetate and bis(dimethylamino)-tert-butoxymethane and treated with various amines and hydrazines to afford the corresponding amino substituted products. Reactions of the titled compound with N,N'-, C,N-, and C,O'-ambident nucleophiles in refluxing acetic acid furnished the corresponding fused pyrimidinones, quinolizinones, and pyranones.     

On the syntheses and some reactions of bis- and tris(methylthio)thiophenes

Reaction between various thienyllithium derivatives and dimethyl disulfide has been used for the preparation of 2,5-, 2,3-, and 3,4-bis(methylthio)thiophenes, as well as 2,3,4- and 2,3,5-tris(methylthio)thiophenes. Bromination of (methylthio)thiophenes with N-bromosuccinimide was found to be most convenient for the preparation of brominated (methylthio)thiophenes such as 3-bromo-2,5-bis(methylthio)- and 5-bromo-2,3-bis(methylthio)thiophene, 3,4-dibromo-2,5-bis(methylthio)-, 2,5-dibromo-3,4-bis(methylthio)- and 2,3-dibromo-4,5-bis(methylthio)thiophene as well as 3-bromo-2,4,5-tris(methylthio)thiophene. The reaction of methylthio substituted thienyllithium derivatives with methyl chloroformate was used for the syntheses of methyl methylthio substituted thiophenecarboxylates and using 1/3 of an equivalent for the direct preparation of methylthio substituted 3-thienylcarbinols as tris[2,4,5-tris(methylthio)-3-thienyl]carbinol.     

Poly-Diels-Alder Addition with a Bisoxazole as Bisdiene and a Bismaleinimide as Bisdienophile

Abstract

The poly-Diels-Alder addition between the new bisdiene 1,4-bis(5-methoxy-2-oxazolyl)benzene (4) and N,N′-hexamethylene-bis[2-(2,5-dihydro-2,5-dioxo-pyrrole-1-yl) acetamide] (7) is described. The structure of the resulting polyadduct 12 was proved by ¹H NMR spectroscopy with the aid of the low-molecular-weight model compounds 1,4-bis(1,3-dihydro-7-hydroxy-1,3-dioxo-2-phenyl-pyrrolo[3,4-c] pyridine-4-yl)benzene (9) and N,N'-hexamethylene-bis[2-(1, 3-dihydro-7-hydroxy-6-methyl-1,3-dioxo-4-phenyl-pyrrolo [3,4-c]pyridine-2-yl)acetamide] (11). The reaction proceeds via the aromatization of the primarily formed cycloadducts. Polyadduct 12 shows a number average degree of polymerization P_n of about 11 – 12 (M_n = 8500 ? 9200 g/mol), calculated from ¹H NMR endgroup signals.     

Synthesis of New Photochromic Dithienylmaleimides with Acetal and Aldehyde Fragments

Reaction of 3,4-dithienylmaleic anhydrides with aminoacetaldehyde dimethylacetal results in the formation of 3,4-dithienyl-substituted 1-(2,2-dimethoxyethyl)-1H-pyrrole-2,5-diones. The hydrolysis of the latter in acid medium results in the preparation of 2-[3,4-bis(thienyl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl]-acetaldehydes. The obtained functionalized derivatives of maleimide demonstrate photochromic properties in solution.     

Synthesis of 1,4-benzothiazin-2-yl derivatives of 1,3-dicarbonyl compounds and benzothiazinone spiro derivatives by the reaction of 2-chloro-1,4-benzothiazin-3-ones with ‘push-pull’ enamines

The reaction of 2-chloro-3-oxo-3,4-dihydro-2H-1,4-benzothiazines with ‘push-pull’ enamines was investigated. The reaction with the enamines occurs at the β-carbon atom in the presence of a small excess of triethylamine. As a result, a set of 3-oxo-3,4-dihydro-2H-1,4-benzothiazin-2-yl derivatives of 1,3-dicarbonyl compounds and benzothiazinone spiro derivatives was prepared. On acidic hydrolysis of ethyl 2-ethyl-3-(methylimino)-2-(3-oxo-3,4-dihydro-2H-1,4-benzothiazin-2-yl)butanoate, a new rearrangement affording ethyl 11-ethyl-2,3-dimethyl-4-oxo-2,3,4,5-tetrahydro-1H-2,5-methano-6,1,3-benzothiadiazocine-11-carboxylate was discovered. A plausible mechanism and factors influencing the course of the reaction are discussed.     

Synthesis of 3-amino-3,4-dihydroquinazolin-4-one derivatives from anthranilic acid hydrazide and dicarboxylic acids

Treatment of anthranilic acid hydrazide with 2 equiv of ethoxalyl chloride gave the corresponding diester which underwent cyclization in acetic anhydride to produce ethyl 3-(ethoxalylamino)-4-oxo-3,4-dihydroquinazoline-2-carboxylate. Acylation of anthranilic acid hydrazide first with succinic anhydride and then with ethoxalyl chloride led to the formation of 4-[2-(2-{[ethoxy(oxo)acetyl]amino}benzoyl)hydrazino]-4-oxobutanoic acid whose cyclization in acetic acid afforded N-(2-ethoxycarbonyl-4-oxo-3,4-dihydroquinazolin-3-yl)succinamic acid, while in acetic anhydride ethyl 3-(2,5-dioxopyrrolidin-1-yl)-4-oxo-3,4-dihydroquinazoline-2-carboxylate was obtained. The latter was brought into reactions with amines and hydrazine hydrate and alkaline hydrolysis. Acylation of 2-[2-(2-aminobenzoyl)hydrazinocarbonyl]benzoic acid with ethoxalyl chloride gave ethyl N-[2-(phthalimidocarbamoyl)phenyl]oxamate, and with succinic anhydride, 3-[4-oxo-3-phthalimido-3,4-dihydroquinazolin-2-yl]propionic acid. 4-[2-(2-Aminobenzoyl)hydrazino]-4-oxobutanoic acid reacted with phthalic anhydride in boiling acetic acid to give phthalazino[1,2-b]quinazoline-5,8-dione via elimination of succinic acid residue.     

Synthesis of 3,4-bis(2,5-dimethyl-3-thienyl)furan-2,5-dione from mucobromic acid

Palladium-catalyzed cross-coupling between 2,5-dimethyl-3-thienylboronic and mucobromic acids under phase transfer catalysis (PTC) conditions gave the expected 3,4-bis(2,5-dimethyl-3-thienyl)-5-hydroxyfuran-2-one in 32% yield. The by-product was 2,2’,5,5’-tetramethyl-3,3’-bithiophene. The oxidation of the obtained hemiacylal with potassium permanganate under PTC conditions afforded 3,4-bis(2,5-dimethyl-3-thienyl)furan-2,5-dione in high yield.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2238–2240, October, 2004.     

Synthesis of π-conjugated poly(arylene)s by polycondensation of 1,4-bis(3-methylpyridin-2-yl)benzene and aryl dibromides through regiospecific C-H functionalization process

On the basis of the Ru-catalyzed regiospecific direct double arylation of benzene rings possessing 3-methylpyridin-2-yl substituents to produce 1-aryl-2-(3-methylpyridin-2-yl)benzene derivatives, the synthesis of poly(p-phenylene) derivatives having 2,5-bis(3-methylpyridin-2-yl) substituents is described. The reaction of 1,4-bis(3-methylpyridin-2-yl)benzene with bromobenzene (2 equiv) was carried out in the presence of [RuCl₂(η⁶-C₆H₆)]₂ (5 mol %) in 1-methyl-2-pyrrolidone at 120°C for 24 h to produce 1,4-bis(3-methylpyridin-2-yl)-2,5-diphenylbenzene in 99% yield as a sole product. Neither 2,6-diphenylated nor further phenylated products was produced under the examined conditions. This regiospecific double arylation process was then applied to the synthesis of π-conjugated polymers by use of aryl dibromides such as 1,4-dibromobenzene, 2,7-dibromo-9,9-dihexylfluorene, and 2,5-dibromothiophene. For example, a polymer was obtained in 73% yield by using 1,4-dibromobenzene, whose M_n and M_w/M_n were estimated to be 3300 and 1.51, respectively. The bathochromic shift of the ultraviolet (UV)–visible absorption spectrum with respect to that of the model compound, 1,4-bis(3-methylpyridin-2-yl)-2,5-diphenylbenzene, indicated the extension of the π-conjugation. The blue fluorescence was also observed for the polymer upon the UV irradiation. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 2771–2777     

New tetrathiafulvalenes containing a 2,5-bis(thiophen-2-yl)pyrrole fragment: Synthesis, optical properties, and electrochemical behavior

The reaction of 1-(3-bromopropyl)-2,5-bis(thiophen-2-yl)-1H-pyrrole with cesium 5-methylsulfanyl-2-thioxo-1,3-dithiole-4-thiolate generated in situ gave previously unknown 4-{3-[2,5-bis(thiophen-2-yl)-1H-pyrrol-1-yl]propylsulfanyl}-5-methylsulfanyl-1,3-dithiole-2-thione, and cross-coupling of the latter with 4,5-disubstituted 1,3-dithiole-2-thiones in the presence of triethyl phosphite afforded new substituted tetrathiafulvalenes containing a 2,5-bis(thiophen-2-yl)pyrrole fragment. Optical properties and electrochemical behavior of the synthesized compounds were studied, and their ability to undergo electropolymerization was confirmed.     

New pyridylphenylene cyclopentadienon as a building block for dendrimer synthesis

Russian Chemical Bulletin - The synthesis of new tetrasubstituted pyridyl-containing cyclopentadienone, namely, 3,4-bis(4-(phenylethynyl)phenyl)-2,5-di(pyridin-2-yl)cyclopenta-2,4-dien-1-one is...